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Vaccine Efficacy, Part 1 of 2: Can a Healthy Diet Improve It?

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The influence of dietary fiber, prebiotics, beta-glucan, and fucoidan

Vaccines are one of the greatest successes of modern medicine, helping to protect entire populations against a wide range of infectious diseases.[1]

A vaccine works by training the immune system to recognize and combat pathogens, either viruses or bacteria. To do this, certain molecules (antigens) from the pathogen are typically introduced into the body to trigger immune cells to produce antibodies.

Unfortunately, even with the best of vaccines, not everyone responds adequately to immunization. Inadequate responses can leave people unknowingly susceptible to new infections even if they are immunized, and may also compromise the achievement of herd immunity in the population.

The efficacy of influenza vaccination, for example, ranges from 20% to 90%, depending on age, study population, and vaccine type.[2] As many as one in four individuals under age 65, and half of those over age 65, do not produce enough antibodies to protect against future infections.[2]

Numerous factors influence whether a particular individual will respond adequately to immunization,[3] including the gut microbiota (the collection of microbes that inhabit the gut.)[4],[5],[6] A healthy microbiota is correlated with a healthy immune response, both to natural infections and vaccines.

In this article we discuss the importance of the microbiota and the influence of dietary fiber, prebiotics, beta-glucan, and fucoidan on vaccine efficacy, and in Part 2 we’ll examine the role of probiotic and synbiotic (prebiotic + probiotic) interventions. Later, we also take a look at the effects of aging (also discussed in a related article about melatonin), and whether immunosenescence can be improved through diet and nutritional measures.

How the microbiota impacts immunity

When the microbiota is healthy it is capable of modulating vaccine efficacy, acting almost like an ‘adjuvant’ to boost vaccine responses.

Billions of microbes inhabit the large intestine, and they strongly influence our health. This community of microbes interacts directly and indirectly with immune cells, influencing the response to infections as well as vaccines.[7],[8] The gut microbiota influences immune responses not only in the gut, but also in the lungs and other organs.[9],[10],[11]

Surprisingly, when the microbiota is healthy it is capable of modulating vaccine efficacy, acting almost like an ‘adjuvant’ to boost vaccine responses.[12],[13] Conversely, when the microbiota is disrupted by antibiotics that kill off normal healthy bacteria, the entire immune system is compromised.[13],[14],[15]

A loss of beneficial bacteria also occurs with low-fiber diets,[16] with many chronic conditions including obesity,[17],[18] and with aging itself.[19],[20] The resulting “dysbiosis” can raise the risk of various infections, and also reduce vaccine efficacy.[21],[22],[23]

On the positive side, regardless of age or comorbidities, the health of the microbiota can be improved with better diets and targeted nutrition. This often translates to better immunity and vaccine efficacy, as we discuss below.[24],[25],[26]

Dietary fiber improves immune responses

Increasing fruit and vegetable intake from two to five servings a day was shown to boost the response to a pneumonia vaccine substantially.

High fiber diets can lower the risk for many diseases, including obesity, diabetes, heart disease, and infections.[27],[28],[29] Experts advise that adults consume at least 21 to 38 grams of fiber daily, depending on age and gender.[27],[28],[29] Unfortunately, 95% of Americans do not achieve these recommended intakes.[27]

Inadequate fiber intakes are associated with a risk of gut dysbiosis and inadequate immune responses,[16],[30],[31],[32] while high-fiber diets increase the abundance of beneficial bacterial species that generate valuable nutrients, including short-chain fatty acids (SCFAs).[33],[34],[35] SCFAs help keep the intestinal wall healthy and they also support the immune system throughout the body.[30],[36],[37],[38] SCFAs are required for optimal health, but their production is frequently limited by the lack of fermentable fiber in the diet.[39],[40]

Increasing one’s fiber intake may reduce mortality from respiratory and infectious diseases,[41] as well as mortality from all causes for that matter.[28] A survey of over 500,000 adults concluded that every 10 gram-per-day increase in dietary fiber intake could lower the risk of death from infectious diseases by 30 to 40%.[41]

Higher dietary fiber intakes may also improve vaccine efficacy. A randomized controlled trial in elderly volunteers, aged 65 to 85, showed that increasing fruit and vegetable (FV) intakes from two to five (three ounce) servings a day could boost the response to a pneumonia vaccine substantially.[42] In fact, just a single serving more a day was predicted to boost the protective antibody response nearly 20%. (For the study, the FV diet was consumed for 12 weeks prior to vaccination and for four weeks after the vaccine was administered.)

In addition to the extensive benefits one may derive from fiber in general, a certain subcategory of fiber known as fermentable fibers, or prebiotics, will be discussed next.

Prebiotics nourish the microbiota

Certain fermentable fibers have been shown to improve vaccine efficacy in animal models and in humans.

Dietary fibers that are fermentable are known as prebiotics, meaning they support the growth of healthy (probiotic) bacteria.[43] In recent years, these fibers have been isolated, characterized, and used to prepare nutritional supplements.

The connection between prebiotics and immunity was clearly demonstrated in a study published in the influential peer-reviewed medical journal Immunity.[44] The authors raised mice on either a high-fiber (HF) diet containing inulin (a fermentable fiber, or prebiotic) or a control diet. The HF diet stimulated the growth of beneficial bacteria in the gut, increased the production of SCFAs, and stimulated white blood cell (WBC) formation in the bone marrow.

The mice were then exposed to influenza virus to generate an infection. In mice fed the HF diet, infection-fighting WBCs found in the lungs had greater antiviral capacity compared to those in control (low-fiber-diet) mice. The mice given the HF diet also had less lung damage and a greater survival rate. The authors note, “By tuning down excessive innate [immune] responses, promoting tissue-protective mechanisms, and stimulating specific adaptive immunity, dietary fiber and SCFAs can create an immune balance that ultimately protects against disease.”[44]

Inulin, and many other prebiotic fiber supplements, have been shown to support the growth of healthy gut bacteria and the production of SCFAs to varying degrees.[43],[45],[46],[47] Additional prebiotics that can be found in foods as well as supplements include fructooligosaccharides (FOS), galactooligosaccharides (GOS), resistant starch, hemicellulose (arabinoxylan), xylooligosaccharides, and β-glucans; and these are just a few.

Certain prebiotics have been shown to improve vaccine efficacy in animal models,[48],[49],[50],[51] and in humans.[52],[53],[54],[55] In one placebo-controlled trial, healthy young adults were supplemented with a prebiotic (long-chain inulin) for two weeks, and were vaccinated against hepatitis B after seven days. On average, the prebiotic group developed higher antibody titers than the placebo group.52 Large clinical trials are needed to validate these findings.

Beyond influencing the microbiota, one class of prebiotics gets high marks when it comes to vaccine strategies, and that is β-glucan.

The special case of beta-glucan

Yeast β-glucan is under investigation as a vaccine adjuvant, as it stimulates antibody production without any known side effects.

β-glucan is a type of polysaccharide found naturally in fungi, including mushrooms and edible yeast (Saccharomyces cerevisiae),[56],[57],[58] and in cereal grains such as oats and barley.[59] The two main types are β-1,3-1,6-glucans (in fungi and yeast) and β-1,3-1,4-glucans (in cereal grains.)

Both types of β-glucans are fermentable,[60],[61] but the structures found in fungi make them much stronger immunomodulators.[62],[63] In fact, fungal β-glucans are unique among prebiotic fibers, as they directly activate the immune system. Many of the health benefits of medicinal mushrooms are attributable to the presence of these immunomodulatory β-glucans.[64],[65]

The reason why immune cells recognize certain β-glucans is quite fascinating. The human immune system is designed to recognize pathogens that might cause infections. To this end, one of the ‘foreign’ molecules that immune cells recognize is β-1,3-1,6-glucan, which is present in the cell walls of yeast including Candida spp.[66],[67],[68] Although certain Candida spp. are considered normal flora in our digestive tract and on numerous epithelial surfaces, it is highly problematic if it enters our blood stream, and warrants an immune response.

Immune cells have receptors that can immediately recognize the β-glucan molecular structure and take action to neutralize the perceived threat.[68],[69],[70] As a bonus, yeast and mushroom β-glucans induce “trained immunity,” a kind of programming of immune cells that confers protection against unrelated infectious agents the body might encounter.[71],[72] In essence, the β-glucan acts as a decoy that fools the immune system into thinking there is a real invader, thus launching the protective immune response.[73] However, β-glucan from food sources is non-toxic and non-infectious.

In animal models, yeast or mushroom β-glucans have been shown to protect against bacterial, parasitic, fungal, and viral infections,[74],[75],[76] including influenza.[77],[78] In randomized controlled trials in healthy adults, supplemental yeast β-glucan has also been shown to reduce the severity of upper respiratory tract infections.[79],[80],[81],[82]

Importantly, the immune response triggered by yeast and mushroom β-glucan additionally may improve vaccine responses, as shown in animals.[83],[84],[85] Yeast β-glucan is even under investigation as a vaccine adjuvant for humans, as it stimulates antibody production without any known side effects.[86],[87],[88],[89] Most β-glucan supplements are prepared from baker’s yeast, S. cerevisiae, which is orally available.[90] As a functional food, yeast β-glucan is listed under the Generally Recognized As Safe (GRAS) category.[91]

Fucoidan

Supplementation with fucoidan for a month prior to vaccination was shown to nearly double the likelihood of achieving protection against future influenza outbreaks.

One more natural product deserves attention here, and that is fucoidan, a polysaccharide derived from seaweed.[62],[93],[94] Fucoidans do not have prebiotic properties,[95] but they modulate the immune system in a manner not unlike that of fungal β-glucans.[96],[97],[98] However, research suggests that fucoidan and β-glucan have additive effects, suggesting they could be used simultaneously.[98]

Fucoidan has been shown to boost innate and adaptive immunity against viruses, bacteria, and vaccines in animal models.[99],[100],[101],[102] In a randomized, placebo-controlled trial of subjects over the age of 60, supplemental fucoidan (300 mg daily for four weeks) was shown to improve the response to a seasonal flu vaccine.[103] In fact, supplementation with fucoidan for a month prior to vaccination was shown to nearly double the likelihood of achieving protection against future influenza outbreaks. Fucoidans have been discussed at length in regard to their immune and antimicrobial properties here, as well as in an interview with PhD chemist, Helen Fitton, who has studied fucoidans and bioactive compounds found in seaweed for many years.

In sum, improving the microbiota through dietary fiber intake can improve overall immunity and vaccine responses. Supplemental prebiotics that are readily fermentable may accelerate this process. Additionally, β-glucan derived from yeast or mushrooms – and fucoidan from seaweed – have direct effects on immune cells, suggesting the possibility of improving vaccine responses through supplementation.

For more on nutrition and vaccine efficacy, stay tuned for these upcoming articles:

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Vaccine Efficacy, Part 2 of 2: Can a Healthy Gut Microbiome Improve It?

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